AU647315B2 - Chlorohexidine adduct and method of preparing same - Google Patents
Chlorohexidine adduct and method of preparing same Download PDFInfo
- Publication number
- AU647315B2 AU647315B2 AU26197/92A AU2619792A AU647315B2 AU 647315 B2 AU647315 B2 AU 647315B2 AU 26197/92 A AU26197/92 A AU 26197/92A AU 2619792 A AU2619792 A AU 2619792A AU 647315 B2 AU647315 B2 AU 647315B2
- Authority
- AU
- Australia
- Prior art keywords
- chlorohexidine
- adduct
- hydrogen fluoride
- salt
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/24—Y being a hetero atom
- C07C279/26—X and Y being nitrogen atoms, i.e. biguanides
- C07C279/265—X and Y being nitrogen atoms, i.e. biguanides containing two or more biguanide groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/16—Fluorine compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/43—Guanidines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Materials For Medical Uses (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A chlorhexidine adduct of one molecule of chlorhexidine with six molecules of hydrogen fluoride and a process for its preparation are described, which adduct has a high antibacterial activity against Streptococcus mutans even in very low concentrations and is useful for the prevention of caries.
<IMAGE>
Description
1 647315
AUSTRALIA
Patents Act 1990 IVOCLAR AG
C
ft ft f
ORIGINAL
COMPLETE SPECIFICATION STANDARD PATENT Invention Title: "Chlorohexidine adduct and method of preparing same" c r fcr o The following statement is a full description of this invention including the best method of performing it known to us:- The invention relates to a chlorohexidine adduct which can be used as an antiseptic and in particular as an antiseptic in dentistry and also as a therapeutic and prophylactic anti-plaque agent.
In the attempt to inhibit or completely stop the formation of plaque and thus also of caries, the effectiveness of substances with antibacterial properties such as e.g. chlorinated phenols, formaldehyde and quaternary ammonium compounds has been examined in S the past. However, they have not been used in practice, because of :0 their toxicity and their restricted action spectrum.
The currently most effective anti-plaque agent is chlorohexidine (1,6-bis-(N-p-chlorophenyl-N'-diguanido)-hexane), which is used in particular in the form of its water-soluble digluconate, but also as sparingly soluble diacetate and dihydrochloride (cf. A. Scheie in J.
Dent. Res. 68, 1609 (1989) and P. Gjermo in J. Dent. Res. 68, 1602 (1989)). Known in addition to these chlorohexidine compounds is also chlorohexidine dihydrofluoride, which according to published German patent application 21 58 150 is used as an antiseptic agent in :20 transparent tooth gels.
It has been shown that chlorohexidine as a chemotherapeutic product is effective against bacteria of the type Streptococcus mutans.
Bacteria of this type play a key part in the formation of caries. It is therefore assumed that, with a reduction of their quantity on the surface of the teeth, caries formation can be countered effectively (cf. I. Ostela and J. Tenovuo in Scand. J. Dent Res. 98, 1 (1990)).
The bactericidal effect exerted by chlorohexidine vis-a-vis bacteria of the type Streptococcus mutans is, however, greatly weakened if it is used in small concentrations. Therefore, chlorohexidine is also subjected to clear restrictions in practical application if it is a matter of reducing tooth plaque which for its part can lead to the occurrence of parodontosis and caries. Moreover, the application of chlorohexidine in higher concentrations can lead to unwanted dis- 3 3 colorations of the tongue, teeth, prostheses and fillings (cf. L.
Fl6tra, P. Gjermo, G. R11a and J. Waerhaug in Scand. J. Dent. Res.
79, 119 (1971)).
It is therefore the object of the invention to make available a chlo-rohexidine adduct which is generally usable as an antiseptic and in particular can be used as an anti-plaque agent, said adduct effec-tively countering the renewal and growth of films on the teeth, even in very small concentrations, and moreover being able, 10 by giving off fluoride, to protect the tooth enamel against demineralization, especially by acids.
This object is achieved by the novel chlorohexidine adduct according to claim 1 and the process for its preparation according to claims :15 2 to 6 as well as its use according to claims 7 and 8.
The chlorohexidine adduct according to the invention is a compound of the following formula: Cl/ NH-C-NH--C-NH-(CH 7 NH-C--NH-C-NH
C
II II II II/ NH NH NH NH 6 HF or its hydrates.
The adduct displays the IR spectrum according to Figure 1. It is not known how the six molecules of hydrogen fluoride in the adduct according to the invention are bound to the chlorohexidine molecule.
It is conceivable in principle that the adduct according to the invention consists of uncharged molecules or is present in the form of ions and thus as salt.
4 The adduct according to the invention is prepared by reacting a solution of hydrogen fluoride with a solution of chlorohexidine salt, the molar ratio of hydrogen fluoride to chlorohexidine salt being at least 6:1, and separating the resultant adduct. If a molar ratio of hydrogen fluoride to chlorohexidine salt of less than 6:1 is used, the adduct according to the invention is also obtained, but in a smaller yield.
The chlorohexidine adduct according to the invention is preferably 10 prepared by reacting a solution of hydrogen fluoride in water with a solution of chlorohexidine .alt in water in a molar ratio of hydrogen fluoride to chlorohexidine salt of 6:1 to 30:1 at a temperature in the range from ambient temperature to reflux temperature, and separating the resulting precipitate.
To achieve high yields and prepare a precipitate of the chlorohexidine adduct according to the invention which is easily separable by filtration, a molar ratio of hydrogen fluoride to chlorohexidine salt of 10:1 to 20:1 is especially preferred. Solutions in a mixture of ethanol/water 90/10 vol.-% are used to advantage at reflux temperature instead of the aqueous solutions of the adducts. In this case, only a molar ratio of hydrogen fluoride to chlorohexidine salt of 8:1 is necessary. The adduct according to the invention is produced in a high yield of more than 95% in this case. Because of the smaller hydrogen fluoride requirement, this variant of the preparation process is especially preferred.
Chlorohexidine digluconate is used preferably for the preparation of the adduct according to the invention. However, other chlorohexidine salts which ari adequately soluble in the solvent used in each case, such as e.g. the dihydrochloride or the diacetate, can also be used.
24 hours are typically adequate as reaction duration in order to achieve a complete reaction. The reaction duration can vary, however, depending on the chosen reaction parameters. However, the 5 reaction duration best suited in each case can easily be ascertained by routine experiments.
The chlorohexidine adduct which occurs predominantly as precipitate during the reaction is preferably separated and cleaned by filtration and subsequent washing with water and acetone. Further chlorohexidine adduct can be obtained by working up the mother liquors, so that overall yields of 91 to nearly 100% are achievable. The puri- .e fied solid is then dried in a known manner and is present, depending on the degree of drying, in the form of hydrates with various water contents. The drying is preferably carried out at 50 0 C in the drying chamber.
Because of its pronounced antibacterial action, the chlorohexidine "15 adduct according to the invention can be used generally as an antiseptic agent. It can be used both in pharmaceutical and cosmetic products as a therapeutic and prophylactic bactericide. However, it is preferably used in dental materials, such as e.g. tooth varnishes, fissure sealants, prophylactic pastes, mouthwashes, toothpicks, dental floss, dental chewing gum, dressings, tooth ointments, gum trainers, disinfectants for prostheses and modelling materials, o• drying agents, underfilling materials, cements, filling materials, adhesion promoters and endodontosis materials. The adduct according to the invention can be deposited on a fixed substrate, such as e.g.
a toothpick or dental floss, or incorporated into dental materials, such as e.g. provisional filling materials and fissure sealants.
Particularly advantageous is the incorporation of the adduct according to the invention into dental materials which are to remain in the oral cavity for a limited period, such as e.g. provisional filling materials, dressings, modelling materials and temporary cements. If the adduct according to the invention is incorporated for example into a provisional filling material, one obtains after its removal a germ-free cavity into which the final filling can be placed immediately.
6 6 As the chlorohexidine adduct displays only quite a low solubility in common solvents, it is preferably incorporated into the said dental materials as a solid. It is added to the dental materials in quantities of 0.1 to 20 preferably 1 to 10 and particularly preferably 3 to 7 relative to the total weight of the material. Examples of usable dental materials are those which contain 10 to 95 of polymerizable organic binder, 5 to 90 wt.of inorganic and/or organic fillers and 0.01 to 5 of catalysts, based on the total weight of the material.
S Solutions containing 0.001 to 0.03 of adduct according to the invention may also be used. Suitable as solvents are, for example, water, ethanol, acetone, ethyl acetate, triethylene glycol dimethacrylate and decandiol methacrylate. Synthetic or natural resins 15 which are soluble in common solvents and become hard after the evaporation of the solvents can also be used. Examples of these are shellac, benzoin resin, polyvinyl pyrrolidone and rosin.
Another preferred application of the chlorohexidine adduct is that as a therapeutic or prophylactic anti-plaque agent. It prevents the renewal of films on teeth and inhibits the growth of already existing films on teeth. Diseases caused by the presence of films on teeth, such as e.g. parodontosis, primary and secondary caries and gingivitis, can thus be combatted effectively with the chlorohexidine adduct according to the invention.
With regard to its bactericidal effectiveness, the adduct according to the invention is completely comparable in a concentration of 0.03 with the chlorohexidine currently rated as a very effective anti-plaque agent. Surprisingly, however, the effectiveness of chlorohexidine is clearly exceeded if both are used in concentrations smaller than or equal to 0.01 In this concentration range, the chlorohexidine adduct according to the invention is also clearly superior to stannous difluoride, a compound which is known for having very good bactericidal properties.
7 The superiority of the adduct according to the invention especially in small concentrations is of particular importance for practical application, as deposited active ingredients are continuously diluted as a result of the permanent saliva flow in the oral cavity. An active ingredient like the chlorohexidine adduct according to the invention, which also displays a marked bactericidal effect in small concentrations, is therefore of particular advantage.
Another advantage compared to chlorohexidine is that, when the 10 adduct according to the invention is used, there are no unwanted side-effects such as a bitter taste, discolorations of tooth materials and irritations of the mucosa.
Finally, the high fluorine content of the adduct according to the 15 invention means that the latter protects the tooth enamel through fluoridation and can therefore also afford effective protection against the formation of caries in this respect.
*99 The invention is explained in more detail in the following examples.
Example 1 To prepare the chlorohexidine adduct according to the invention, 42.5 ml of an aqueous 20% (0.01 mole) chlorohexidine digluconate solution were added under stirring dropwise within 2 hours to 45 ml of an aqueous 4.4% (0.11 mole) HF solution. The mixture was stirred further overnight, and the precipitate which formed was filtered and washed threetimes with 50 ml of water each time and then twice with ml of acetone each time. The resultant precipitate was then dried at 50 0 C in the drying chamber. The chlorohexidine adduct according to the invention was obtained as a solid in a yield of 76% and had a melting point of 185 to 1900C.
The IR spectrum (KBr moulding) is reproduced in Fig. 1.
8 8 Elementary analysis shows that the product is chlorohexidine hexahydrofluoride with one to two moles of crystal water.
Structure A:
C
22 H30 Ni C1 6HF HzO Structure B:
C
22
H
30
N
0 i Cl 2 6HF 2H20 Elementary analysis: .i
LO
C
H
N
Cl
F
H20 found 41.00% 5.15% 21.70% 10.85% 17.55% 3.75% Structure MW 642.9 MW 660.9 theoretical A Structure B 39.95% 5.45% 21.18% 10.73% 17.25% 5.45% 41.06% 5.60% 21.78% 11.02% 17.73% 2.80%
S..
5
H
2 0 content determined by the Karl Fischer method The solubility of the adduct according to the invention in some common solvents and reactive diluents is given in the following Table I:
S..
S. S.
9 9 Table I Water (pH value 2 to 9.7) 0.03 wt.-% Ethanol 0.005 wt.-% Acetone 0.03 wt.-% Ethyl acetate 0.02 wt.-% Triethylene glycol dimethacrylate (SR-205) 0.005 wt.-% S Decandiol dimethacrylate (D 3 MA) 0.005 wt.-% •Example 2 By using 90 ml of an aqueous 4.4% (0.2 mole) HF solution and 42.5 ml of an aqueous 20% (0.01 mole) chlorohexidine digluconate solution the reaction procedure otherwise being the same as in Example 1 a S"precipitate was obtained which was more easily filterable than the 20 one obtained according to Example 1.
The chlorohexidine adduct was obtained in a higher yield of 91 to 94%.
25 Example 3 42.5 ml (0.01 mole) of an aqueous 20% chlorohexidine digluconate solution were added dropwise to 200 ml (0.08 mole) of a solution of hydrogen fluoride in a 90/10 vol.-% mixture of ethanol/water at reflux temperature for 1 hour, accompanied by stirring, and the stirring was continued for a further hour. After the reaction mixture had cooled to ambient temperature the resultant precipitate was filtered off and washed threetimes, each time with 50 ml of a 90/10 vol.-% mixture of ethanol/water. In contrast to the preparation processes carried out at ambient temperature as in Example 1 and Example 2, the resultant precipitate was crystalline and thus easily filterable. Further product came out of the mother liquor within a further week. The total yield was 98%.
10 Compared to the process variants according to Examples 1 and 2, the advantage with this process procedure in a mixture of ethanol/water at reflux temperature is that a better filterable precipitate occurs in a very high yield and the hydrogen fluoride requirement is much smaller.
Example 4 o The antibacterial effectiveness of the chlorohexidine adduct 10 according to the invention was demonstrated in the Agar diffusion test with Streptococcus mutans.
For this purpose, culture suspensions of Streptococcus mutans were added to a liquid Agar comprising yeast extract and dextrose. After 15 the Agar plates had solidified, a hole of 10 mm diameter was cut out, into which 0.1 ml of the solution to be tested was poured in each case. After 24 hours of incLoation at 37 0 C, the diameters of S the inhibiting zones were measured for each sample, which were duplicated in each case. The results of these tests are reproduced in the following Table II.
Table II Inhibiting zone diameters Concentration Solution A Solution B Solution C 0.03 17 mm 17 mm 20 mm 0.01 13 mm 15 mm 11 mm 0.003 11 mm 12 mm 10 mm* Not effective Solution A: Aqueous solution of chlorohexidine digluconate Solution B: Aqueous solution of the chlorohexidine adduct according to the invention Solution C: Aqueous solution of stannous difluoride 11 11 It transpires that in the concentration range of 0.03 the antibacterial effectiveness of the chlorohexidine adduct according to the invention vis-a-vis Streptococcus mutans is comparable with that of chlorohexidine gluconate, while stannous difluoride displays an even stronger action in this concentration range. However, increasing dilution is accompanied by markedly declining effectiveness in the case of the known compounds, to such an extent indeed in the case of stannous difluoride at a concent:ation of 0.003 that an antibacterial action can no longer be detected. Compared to this, .:10 the antibacterial effectiveness of the adduct according to the invention is still very high even at concentration- of 0.01 to 0.003 Its superiority especially in low concentrations thus makes it a very effective anti-plaque agent.
Example A light-curable fissure sealant contains the following constituents: 56.08 bisphenol A glycidyl methacrylate (Bis-GMA) :20 36.1 triethylene glycol dimethacrylate 0.45 cyanoethylmethylaniline 0.25 DL-camphor quinone 2.1 TiO 2 S* 0.02 2,6-di-tert.-butyl-p-cresol 5.0 chlorohexidine adduct The light-curable fissure sealant was obtained by mixing all the components. The sealant was applied with a brush onto the fissures in a molar tooth and hardened for 20 sec with the Heliolux® lightcurable apparatus made by Vivadent/Liechtenstein. In this way the fissures were permanently sealed and, because of the fluoride liberated by the chlorohexidine adduct incorporated into the sealant, excellent protection against caries was achieved in the occlusal area.
As a result of the admixture of 1 to 5 of the chlorohexidine adduct to the basic fissure-sealant formulation, no decrease in 12 12 through-hardening depth was observed, as the following values for Vickers hardness show: Fissure sealant without chlorohexidine adduct Fissure sealant 1% chlorohexidine addact Fissure sealant 3% chlorohexidine adduct Fissure sealant 5% chlorohexidine adduct HV 188 MPa 248 MPa 212 MPa 180 MPa 0 0 a as .00.
0 so To detect chlorohexidine and fluoride migration, 10 test specimens, each 50 mm in diameter and 0.5 mm high, were stored in dist. water at 37 0 C. The fluoride ion concentration was determined by means of a fluoroelectrode and the chlorohexidine concentration was ascertained by means of UV spectroscopy. The cumulative figure for liberated fluoride and chlorobxidine is summarized in Table III.
Table III 5.55 2 20 a 0 25 g Migration time [days] Fluoride liberated Chlorohexidine liberated [lg/cm 2 0.95 1.48 1.91 2.22 2.91 3.45 4.22 4.92 5.58 6.56 [pg/cma] 3.86 5.56 6.84 7.58 9.26 10.30 11.60 12.30 13.20 14.40 The results are represented graphically in Figures 2 and 3.
13 13 Example 6 A light-curable dental material with relatively high water absorption and thus high active ingredient release suitable as provisional filling material or as a dressing) has the following composition: 43.6 polyester urethane dimethacrylate 0.25 cyanoethylmethylaniline 0.15 DL-camphor quinone 35.0 splinter polymerizate 21.0 amorphous SiO 2 silanized (BET surface 50 m 2 /g) The splinter polymerizate comprises: 59.4 urethane dimethacrylate -:ine-particled SiO 2 silanized 0.6 benzpinacol.
20 The components are mixed together and polymerized at 120 0 C. The filled polymerizate is ground into a polymer powder.
The amorphous fine-particled silanized SiOz is Aerosil® OX 50 from Degussa AG.
A light-curable dental material was obtained by mixing all the components.
The water absorption of dental filling composites is normally in the range of 1 this material displays a water absorption in the range of 3 (3 weeks H7O storage at 37 0 The cumulative amount of fluoride and chlorohexidine liberated is summarized in Table IV.
14 14 Table IV 0..
25 Migration time [days] 1 2 3 4 7 17 24 4 Fluoride given off Chlorohexidine given off [ug/cm 2 [Ig/cm 2 3.78 17.0 6.03 25.7 8.03 33.6 9.82 40.3 11.98 51.4 13.99 60.6 16.37 74.5 18.68 86.6 19.88 97.8 22.68 118.3 The results are represented graphically in Figures 2 and 3.
As the migration tests show, significant quantities of fluoride and chlorohexidine are released from this dental material, so that an adequate inhibition of the growth of microorganisms is also to be expected in this combination.
Since not all microorganisr react identically to released active ingredients, studies were conducted using the following microbes.
Gram-positive bacteria: Gram-negative bacteria: Streptococcus mutans Staphylococcus aureus Pseudomonas auruginosa Escherichia coli Fungus: Candida albicans Test specimens (d 10 mm, h 2 mm) were inserted into the moist microorganism cultures at 37 0 C over a period of 24 hours and the inhibiting zone was then determined.
15 Inhibiting zone diameter [mm] Streptococcus mutans Staphylococcus aureus lo Pseudomonas auruginosa 17 Escherichia coli Candida albicans 12 A clear inhibition of growth can be established for these different microorganisms.
*ee ee a e a *o* 16
Claims (9)
1. Chlorohexidine adduct having the following formula CtL NH-C-NH-C-N -NH-(CH -NH-C-NH-C-NH-Y Cl NH NH NH NH '6 HF and its hydrates.
2. Process for preparing the chlorohexidine adduct according to "*claim 1, wherein a) a solution of hydrogen fluoride is reacted with a solution of a chlorohexidine salt, b) the molar ratio of hydrogen fluoride to chlorohexidine I salt being at least 6:1, and c) the resultant adduct is separated.
3. Process according to claim 2, wherein a) aqueous solutions are used, b) the molar ratio of hydrogen fluoride to chlorohexidine salt is 6:1 to 30:1 and c) the reaction is carried out at a temperature in the range from 20 0 C to reflux t,-oerature.
4. Process according to claim 2, wherein 17 17 a) solutions in a mixture of ethanol and water are used, b) the molar ratio of hydrogen fluoride to chlorohexidine salt is at least 8:1 and c) the conversion is carried out at reflux temperature.
5. Process according to claim 4, wherein a 90/10 vol.-% mixture of ethanol and water is used in step a). 6
6. Process according to one of claims 2 to 4, wherein chloro- hexidine digluconate is used as chlorohexidine salt. .a
7. An antiseptic composition comprising the chlorohexidine adduct or its hydrates according to claim 1. 15
8. An anti-plaque composition for the prevention of caries com- prising the chlorohexidine adduct or its hydrates according to claim 1. DATED THIS 2nd DAY OF OCTOBER 1992 IVOCLAR AG Patent Attorneys for the Applicant:- F.B. RICE CO. ABSTRACT A chlorohexidine adduct comprising one molecule of chlorohexidine with six molecules of hydrogen fluoride and a process for its preparation are described, said adduct displaying a high anti- bacterial effectiveness vis-a-vis Streptococcus mutans even in very small concentrations and being valuable as anti-plaque agent and for caries prevention.
.9 *5o* frT V* V
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4135397 | 1991-10-26 | ||
DE4135397A DE4135397C2 (en) | 1991-10-26 | 1991-10-26 | Chlorhexidine adduct, process for its preparation and its use |
Publications (2)
Publication Number | Publication Date |
---|---|
AU2619792A AU2619792A (en) | 1993-04-29 |
AU647315B2 true AU647315B2 (en) | 1994-03-17 |
Family
ID=6443511
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU26197/92A Ceased AU647315B2 (en) | 1991-10-26 | 1992-10-02 | Chlorohexidine adduct and method of preparing same |
Country Status (6)
Country | Link |
---|---|
US (1) | US5304369A (en) |
EP (1) | EP0539811B1 (en) |
AT (1) | ATE136294T1 (en) |
AU (1) | AU647315B2 (en) |
CA (1) | CA2079561C (en) |
DE (2) | DE4135397C2 (en) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4222821C2 (en) * | 1992-07-08 | 1994-09-22 | Ivoclar Ag | Modified chlorhexidine adduct |
EP1123060B1 (en) * | 1998-09-24 | 2008-04-23 | Advantage Dental Products Inc. | Calcified tissue facing preparation containing an antimicrobial agent |
US6726899B2 (en) | 1998-09-24 | 2004-04-27 | Advantage Dental Products, Inc. | Calcified tissue facing preparation containing antimicrobial agent |
DE19921950A1 (en) * | 1999-05-12 | 2000-11-16 | Susanne Szep | Dentine adhesives containing hydrogen fluoride for use in dental restorative work |
DE19921727A1 (en) * | 1999-05-12 | 2000-11-16 | Susanne Szep | Fluoriding composition for treating tooth surfaces to prevent caries and reduce sensitivity, containing hydrogen fluoride to form strongly bound fluoride complexes on surface |
US20060254988A1 (en) * | 2005-05-10 | 2006-11-16 | Confirm Monitoring Systems, Inc. | Methods and compositions for the treatment of water |
RU2696259C2 (en) | 2017-10-23 | 2019-08-01 | Общество С Ограниченной Ответственностью "Сан Системз" | Solubilization of the chlorhexidine base, antiseptic and disinfectant compositions |
DE102019000322A1 (en) | 2019-01-14 | 2020-07-16 | Beuth Hochschule Für Technik Berlin | Polymer composition with antiseptic properties and method of manufacture |
DE102019000321A1 (en) | 2019-01-14 | 2020-07-16 | Beuth Hochschule Für Technik Berlin | Oral sustained release polymer composition |
DE102020007979A1 (en) | 2020-12-29 | 2022-06-30 | Charité Universitätsmedizin Institut für Mikrobiologie und Infektionsimmunologie | Composition for treating coronavirus infections |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0110568A1 (en) * | 1982-10-29 | 1984-06-13 | The Procter & Gamble Company | Oral compositions |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AT211511B (en) * | 1958-09-12 | 1960-10-25 | Bbc Brown Boveri & Cie | Device for electric shaft hoisting machines for retarding to any shaft point |
GB1304090A (en) * | 1970-11-27 | 1973-01-24 | ||
GB1369942A (en) * | 1971-11-03 | 1974-10-09 | Colgate Palmolive Co | Antibacterial biguanide salts |
DE2430280A1 (en) * | 1973-07-27 | 1976-01-08 | Blendax Werke Schneider Co | Toothpaste and mouth-wash which are used consecutively - respectively contg urea and anion-active tenside phase and 1,6-di-4'-chlorophenyl-di-guanido-hexane phase |
-
1991
- 1991-10-26 DE DE4135397A patent/DE4135397C2/en not_active Expired - Fee Related
-
1992
- 1992-09-30 CA CA002079561A patent/CA2079561C/en not_active Expired - Fee Related
- 1992-10-02 AU AU26197/92A patent/AU647315B2/en not_active Ceased
- 1992-10-16 EP EP92117719A patent/EP0539811B1/en not_active Expired - Lifetime
- 1992-10-16 AT AT92117719T patent/ATE136294T1/en not_active IP Right Cessation
- 1992-10-16 DE DE59205899T patent/DE59205899D1/en not_active Expired - Fee Related
- 1992-10-23 US US07/965,019 patent/US5304369A/en not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0110568A1 (en) * | 1982-10-29 | 1984-06-13 | The Procter & Gamble Company | Oral compositions |
Also Published As
Publication number | Publication date |
---|---|
DE4135397A1 (en) | 1993-04-29 |
CA2079561C (en) | 1997-01-07 |
DE4135397C2 (en) | 1994-01-20 |
EP0539811A3 (en) | 1993-07-28 |
EP0539811B1 (en) | 1996-04-03 |
DE59205899D1 (en) | 1996-05-09 |
AU2619792A (en) | 1993-04-29 |
CA2079561A1 (en) | 1993-04-27 |
US5304369A (en) | 1994-04-19 |
ATE136294T1 (en) | 1996-04-15 |
EP0539811A2 (en) | 1993-05-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU655547B2 (en) | Modified chlorhexidine-adduct | |
EP0128655B1 (en) | Benzoin antimicrobial dental varnishes | |
EP0264660B1 (en) | Use of a dental material for combating caries and periodontosis | |
JPS60233008A (en) | Oral sanitary composition | |
AU647315B2 (en) | Chlorohexidine adduct and method of preparing same | |
JP2975380B2 (en) | Plaque formation inhibitor | |
US4820507A (en) | Oral and dental hygiene preparations | |
EP2249764B1 (en) | Tooth sealant | |
JPH04257511A (en) | Antibacterial oral composition free from pollution | |
US20010009931A1 (en) | Protective varnish for dentin | |
AU2019304199A1 (en) | Amino acid containing oral care composition for treating caries by reducing lactic acid release in oral biofilms | |
KR20190095156A (en) | Composition for preventing or treating periodontal disease and dental caries containing fluoride varnish and antibacterial agents as an active ingredient | |
CA2288331A1 (en) | Antimicrobial dental materials containing 2,4,4'-trichloro-2'-hydroxydiphenyl ether | |
JPS6216923B2 (en) | ||
WO2003086359A1 (en) | Tea polyphenol buccal tablet for preventing and treating tooth decay and its preparing method | |
EP0373429A2 (en) | Oral treatment method for reducing plaque with reduced staining | |
US4020019A (en) | Anticaries agents | |
US20020012634A1 (en) | Antimicrobial dental materials contraining 2,4,4' -trichloro2' -hydroxydiphenyl ether | |
RU2200541C2 (en) | Remedy for hygiene of oral cavity | |
EP3848017A1 (en) | Oral care composition containing indole components for treating caries | |
JPH09502998A (en) | Substantially antibacterial phosphate | |
EP3848016A1 (en) | Oral care composition containing fatty acid components for treating caries | |
JPH0560444B2 (en) | ||
WO2021140437A1 (en) | Anionic alkyl sulphate component for treating caries | |
JP2002205929A (en) | Composition for oral cavity |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |